The long-term goal of the proposed research is to develop an understanding of the transport of ions in the mammary epithelium. During the proposed project period a comprehensive attack will be mounted on the regulation of the monovalent ion content of milk, the role of calcium in the regulation of mammary cell function and the regulation of the junctional complexes which control the "leakiness" of the mammary epithelium. These problems will be approached (1) using electrophysiological techniques in both an in vivo mouse preparation recently shown to be suitable for such studies and in cultured mammary epithelium (2) using membrane vesicles purified by a combination of sorbitol density gradient and counter current distribution techniques and (3) in the intact, conscious lactating goat. These preparations will be used to test a new hypothesis for monovalent cation transport, to continue studies on calcium transport and to initiate studies of a physiological factor involved in the regulation of junctional complexes. These preparations should allow a truly quantitative approach to the many transport problems presented by this unique and complex epithelial tissue. The American Academy of Pediatrics has recommended breast milk as the food most suited for the first six months of human life. For this reason it is important that we understand the mechanisms by which the composition of milk is regulated.